Journal Article

Antiretroviral Drug Concentrations and HIV RNA in the Genital Tract of HIV-Infected Women Receiving Long-Term Highly Active Antiretroviral Therapy

Awewura Kwara, Allison DeLong, Naser Rezk, Joseph Hogan, Heather Burtwell, Stacy Chapman, Carla C. Moreira, Jaclyn Kurpewski, Jessica Ingersoll, Angela M. Caliendo, Angela Kashuba and Susan Cu-Uvin

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 46, issue 5, pages 719-725
Published in print March 2008 | ISSN: 1058-4838
Published online March 2008 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/527387
Antiretroviral Drug Concentrations and HIV RNA in the Genital Tract of HIV-Infected Women Receiving Long-Term Highly Active Antiretroviral Therapy

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Objective. Our objective was to determine antiretroviral drug concentrations and human immunodeficiency virus (HIV) RNA rebound in cervicovaginal fluid (CVF) in relation to blood plasma (BP) in women receiving suppressive highly active antiretroviral therapy (HAART).

Methods. Thirty-four HIV-infected women who had plasma HIV RNA levels ⩽80 copies/mL for at least 6 months were enrolled. Sixty-eight paired CVF and BP drug concentrations and HIV RNA levels were determined before and 3–4 h after drug administration. For each woman and antiretroviral drug, the CVF:BP drug concentration ratios before and after drug administration were calculated. The nonparametric Wilcoxon rank sum test was used to determine if these ratios were different from 1.0.

Results. Lamivudine (administered to 20 patients) and tenofovir (administered to 16) had significantly higher concentrations in CVF than in BP before drug administration, with mean CVF:BP concentration ratios of 3.19 (95% confidence interval, 1.2–8.5) and 5.2 (95% confidence interval, 1.2–22.6), respectively. Efavirenz (administered to 13 patients) and lopinavir (administered to 6) had significantly lower concentrations in CVF, with mean CVF:BP concentration ratios of 0.01 (95% confidence interval, 0.00–0.03) and 0.03 (0.01–0.11), respectively. During the study visit (median time after enrollment, 6 months), BP and CVF detectable HIV RNA levels were observed 7 patients (20.6%) and 1 patient (2.9%), respectively.

Conclusion. Despite lower CVF concentrations of key HAART components, such as efavirenz and lopinavir, virologic rebound was rare. The high concentrations of tenofovir and lamivudine in CVF may have implications for the prevention of sexual transmission during HAART and for pre-exposure or postexposure prophylaxis.

Journal Article.  4102 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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